tbuckley/cabot-search huggingface dataset:
iPSC-Based Modeling of Variable Clinical Presentation in Hypertrophic Cardiomyopathy
Authors: Rubén Escribá, José M. Larrañaga-Moreira, Yvonne Richaud-Patin, Léa Pourchet, Ioannis Lazis, Senda Jiménez-Delgado, Alba Morillas-García, Martín Ortiz-Genga, Juan Pablo Ochoa, David Carreras, Guillermo Javier Pérez, José Luis de la Pompa, Ramón Brugada, Lorenzo Monserrat, Roberto Barriales-Villa, Angel Raya
Journal: Circulation Research (2023)

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease and a frequent cause of heart failure and sudden cardiac death. Our understanding of the genetic bases and pathogenic mechanisms underlying HCM has improved significantly in the recent past, but the combined effect of various pathogenic gene variants and the influence of genetic modifiers in disease manifestation are very poorly understood. Here, we set out to investigate genotype-phenotype relationships in 2 siblings with an extensive family history of HCM, both carrying a pathogenic truncating variant in the MYBPC3 gene (p.Lys600Asnfs*2), but who exhibited highly divergent clinical manifestations.We used a combination of induced pluripotent stem cell (iPSC)-based disease modeling and CRISPR (clustered regularly interspersed short palindromic repeats)/Cas9 (CRISPR-associated protein 9)-mediated genome editing to generate patient-specific cardiomyocytes (iPSC-CMs) and isogenic controls lacking the pathogenic MYBPC3 variant.Mutant iPSC-CMs developed impaired mitochondrial bioenergetics, which was dependent on the presence of the mutation. Moreover, we could detect altered excitation-contraction coupling in iPSC-CMs from the severely affected individual. The pathogenic MYBPC3 variant was found to be necessary, but not sufficient, to induce iPSC-CM hyperexcitability, suggesting the presence of additional genetic modifiers. Whole-exome sequencing of the mutant carriers identified a variant of unknown significance in the MYH7 gene (p.Ile1927Phe) uniquely present in the individual with severe HCM. We finally assessed the pathogenicity of this variant of unknown significance by functionally evaluating iPSC-CMs after editing the variant.Our results indicate that the p.Ile1927Phe variant of unknown significance in MYH7 can be considered as a modifier of HCM expressivity when found in combination with truncating variants in MYBPC3. Overall, our studies show that iPSC-based modeling of clinically discordant subjects provides a unique platform to functionally assess the effect of genetic modifiers.
Calcium carbonate nanoparticles tumor delivery for combined chemo-photodynamic therapy: Comparison of local and systemic administration
Authors: Anastasiya A. Yakubova, Ksenia A. Mitusova, Aya Darwish, Anna Rogova, Eduard I. Ageev, Aleksandra Brodskaia, Albert R. Muslimov, Mikhail V. Zyuzin, Alexander S. Timin
Journal: Journal of Controlled Release (2023)
Rare cases of Guillain-Barré syndrome after COVID-19 vaccination, Germany, December 2020 to August 2021
Authors: Helmar C Lehmann, Doris Oberle, Brigitte Keller-Stanislawski, Thorsten Rieck, Renz Streit
Journal: Eurosurveillance (2023)

Background Guillain-Barré syndrome (GBS) has been associated with vaccination against COVID-19. Aim We aimed to compare clinical characteristics and analyse excess GBS cases following administration of different COVID-19 and influenza vaccines in Germany versus the expected numbers estimated from pre-pandemic background incidence rates. Methods We analysed safety surveillance data reported to the German national competent authority between 27 December 2020 and 31 August 2021. GBS cases were validated according to Brighton Collaboration (BC) criteria. We conducted observed vs expected (OvE) analyses on cases fulfilling BC criteria levels 1 to 4 for all four European Medicines Agency-approved COVID-19 vaccines and for influenza vaccines. Results A total of 214 GBS cases after COVID-19 vaccination had been reported, of whom 156 were eligible for further analysis. Standardised morbidity ratio estimates 3–42 days after vaccination were 0.34 (95% confidence interval (CI): 0.25–0.44) for Comirnaty, 0.38 (95% CI: 0.15–0.79) for Spikevax, 3.10 (95% CI: 2.44–3.88) for Vaxzevria, 4.16 (95% CI: 2.64–6.24) for COVID-19 Vaccine Janssen and 0.60 (95% CI: 0.35–0.94) for influenza vaccines. Bilateral facial paresis was reported in 19.7% and 26.1% of the 156 GBS cases following vaccination with Vaxzevria and COVID-19 Vaccine Janssen, respectively, and only in 6% of cases exposed to Comirnaty. Conclusion Three and four times more GBS cases than expected were reported after vaccination with Vaxzevria and COVID-19 Vaccine Janssen, respectively, therefore GBS might be an adverse event of vector-based vaccines. Bifacial paresis was more common in cases with GBS following vaccination with vector-based than mRNA COVID-19 vaccines.
Fulminant echovirus 11 hepatitis in male non-identical twins in northern Italy, April 2023
Authors: Antonio Piralla, Alessandro Borghesi, Amelia Di Comite, Federica Giardina, Guglielmo Ferrari, Simona Zanette, Tiziana Angelica Figar, Micol Angelini, Camilla Pisoni, Antonino Maria Guglielmo Pitrolo, Stefania Paolucci, Francesca Rovida, Isabella Pellicioli, Ezio Bonanomi, Fausto Baldanti, Stefano Ghirardello
Journal: Eurosurveillance (2023)

Echovirus 11 (E11) has recently been associated with a series of nine neonatal cases of severe hepatitis in France. Here, we present severe hepatitis caused by E11 in a pair of twins. In one of the neonates, the clinical picture evolved to fulminant hepatitis. The E11 genome showed 99% nucleotide identity with E11 strains reported in the cases in France. Rapid genome characterisation using next generation sequencing is essential to identify new and more pathogenetic variants.
PNOC015: Repeated convection-enhanced delivery of MTX110 (aqueous panobinostat) in children with newly diagnosed diffuse intrinsic pontine glioma
Authors: Sabine Mueller, Cassie Kline, Schuyler Stoller, Shannon Lundy, Lauren Christopher, Alyssa T Reddy, Anu Banerjee, Tabitha M Cooney, Shannon Raber, Carly Hoffman, Tracy Luks, Eva Wembacher-Schroeder, Nina Lummel, Yalan Zhang, Erin R Bonner, Javad Nazarian, Annette M Molinaro, Michael Prados, Javier E Villanueva-Meyer, Nalin Gupta
Journal: Neuro-Oncology (2023)

Abstract Background The objective of this study was to determine the safety, tolerability, and distribution of MTX110 (aqueous panobinostat) delivered by convection-enhanced delivery (CED) in patients with newly diagnosed diffuse intrinsic pontine glioma (DIPG) who completed focal radiation therapy (RT). Methods Patients with DIPG (2–21 years) were enrolled after RT. CED of MTX110 combined with gadoteridol was completed across 7 dose levels (DL) (30–90 µM; volumes ranging from 3 mL to 2 consecutive doses of 6 mL). An accelerated dose escalation design was used. Distribution of infusate was monitored with real-time MR imaging. Repeat CED was performed every 4–8 weeks. Quality-of-life (QoL) assessments were obtained at baseline, every 3 months on therapy, and end of therapy. Results Between May 2018 and March 2020, 7 patients who received a total of 48 CED infusions, were enrolled (median age 8 years, range 5–21). Three patients experienced dose-limited toxicities. Four grade 3 treatment-related adverse events were observed. Most toxicities were transient new or worsening neurologic function. Median overall survival (OS) was 26.1 months (95% confidence interval: 14.8–not reached). Progression-free survival was 4–14 months (median, 7). Cumulative percentage of tumor coverage for combined CED infusions per patient ranged from 35.6% to 81.0%. Increased CED infusions were negatively associated with self-reported QoL assessments. Conclusion Repeat CED of MTX110 with real-time imaging with gadoteridol is tolerable for patients with DIPG. Median OS of 26.1 months compares favorably with historical data for children with DIPG. The results support further investigation of this strategy in a larger cohort.
Tuberculosis in times of war and crisis: Epidemiological trends and characteristics of patients born in Ukraine, Germany, 2022
Authors: Barbara Hauer, Stefan Kröger, Walter Haas, Bonita Brodhun
Journal: Eurosurveillance (2023)

The Russian invasion of Ukraine in 2022 caused a large migration to other European countries, including Germany. This movement impacted the TB epidemiology, as Ukraine has a higher prevalence of TB and multidrug-resistant TB rates compared to Germany. Our descriptive analysis of TB surveillance data reveals important information to improve TB care in people displaced from Ukraine. We observed an expected increase in the number of TB patients born in Ukraine, which is, however, so far below WHO/Europe estimates.
Granular Hydrogels in Biofabrication: Recent Advances and Future Perspectives
Authors: Andrew C. Daly
Journal: Advanced Healthcare Materials (2023)

Granular hydrogels, which are formed by densely packing microgels, are promising materials for bioprinting due to their extrudability, porosity, and modularity. However, the multidimensional parameter space involved in granular hydrogel design makes material optimization challenging. For example, design inputs such as microgel morphology, packing density, or stiffness can influence multiple rheological properties that govern printability and the behavior of encapsulated cells. This review provides an overview of fabrication methods for granular hydrogels, and then examines how important design inputs can influence material properties associated with printability and cellular responses across multiple scales. Recent applications of granular design principles in bioink engineering are described, including the development of granular support hydrogels for embedded printing. Further, the paper provides an overview of how key physical properties of granular hydrogels can influence cellular responses, highlighting the advantages of granular materials for promoting cell and tissue maturation after the printing process. Finally, potential future directions for advancing the design of granular hydrogels for bioprinting are discussed.
Pulmonary Artery Catheter Use and Mortality in the Cardiac Intensive Care Unit
Authors: Bernard S. Kadosh, David D. Berg, Erin A. Bohula, Jeong-Gun Park, Vivian M. Baird-Zars, Carlos Alviar, James Alzate, Christopher F. Barnett, Gregory W. Barsness, James Burke, Sunit-Preet Chaudhry, Lori B. Daniels, Andrew DeFilippis, Anthony Delicce, Christopher B. Fordyce, Shahab Ghafghazi, Umesh Gidwani, Michael Goldfarb, Jason N. Katz, Ellen C. Keeley, Benjamin Kenigsberg, Michael C. Kontos, Patrick R. Lawler, Evan Leibner, Venu Menon, Thomas S. Metkus, P. Elliott Miller, Connor G. O’Brien, Alexander I. Papolos, Rajnish Prasad, Kevin S. Shah, Shashank S. Sinha, R. Jeffrey Snell, Derek So, Michael A. Solomon, Bradley W. Ternus, Jeffrey J. Teuteberg, Joseph Toole, Sean van Diepen, David A. Morrow, Robert O. Roswell
Journal: JACC Heart Failure (2023)
Effect of 6-Month HIV Preexposure Prophylaxis Dispensing With Interim Self-testing on Preexposure Prophylaxis Continuation at 12 Months
Authors: Katrina F. Ortblad, Ashley R. Bardon, Peter Mogere, Catherine Kiptinness, Stephen Gakuo, Sarah Mbaire, Katherine K. Thomas, Nelly R. Mugo, Jared M. Baeten, Kenneth Ngure
Journal: JAMA Network Open (2023)

Importance Daily oral HIV preexposure prophylaxis (PrEP) delivery requires quarterly clinic visits for HIV testing and drug refilling that are costly to health systems and clients. Objective To evaluate whether 6-month PrEP dispensing supported with interim HIV self-testing (HIVST) results in noninferior PrEP continuation outcomes at 12 months compared with standard quarterly clinic visits. Design, Setting, and Participants This randomized noninferiority trial was conducted from May 2018 to May 2021 with 12 months of follow-up among PrEP clients aged 18 years or older who were returning for their first refill at a research clinic in Kiambu County, Kenya. Intervention Participants were randomized 2:1 to (1) 6-month PrEP dispensing with semiannual clinic visits and interim HIVST at 3 months or (2) standard-of-care (SOC) PrEP delivery with 3-month dispensing, quarterly clinic visits, and clinic-based HIV testing. Main Outcomes and Measures Prespecified 12-month outcomes included recent HIV testing (any in past 6 months), PrEP refilling, and PrEP adherence (detectable tenofovir-diphosphate concentrations in dried blood spots). Binomial regression models were used to estimate risk differences (RDs), and a 1-sided 95% CI lower bound (LB) of −10% or greater was interpreted as noninferior. Results A total of 495 participants were enrolled, with 329 enrolled in the intervention group and 166 enrolled in the SOC group; 330 (66.7%) were women, 295 (59.6%) were in serodifferent relationships, and the median (IQR) age was 33 (27-40) years. At 12 months, 241 individuals in the intervention group (73.3%) and 120 in the SOC group (72.3%) returned to clinic. In the intervention group, recent HIV testing was noninferior (230 individuals [69.9%]) compared with the SOC group (116 [69.9%]; RD, −0.33%, 95% CI LB, −7.44%). PrEP refilling in the intervention group (196 [59.6%]) was inconclusive compared with the SOC group (104 [62.7%]; RD, −3.25%; 95% CI LB, −10.84%), and PrEP adherence was noninferior in the intervention group (151 [45.9%]) compared with the SOC group (70 [42.2%]; RD, 4.96%; 95% CI LB, −2.46%). No HIV seroconversions were observed over the follow-up period. Conclusions and Relevance In this analysis of secondary trial end points at 1 year, semiannual PrEP dispensing with interim HIVST resulted in noninferior recent HIV testing and PrEP adherence compared with SOC quarterly PrEP dispensing. This novel model has the potential to optimize PrEP delivery. Trial Registration ClinicalTrials.gov Identifier: NCT03593629
Orally-delivered insulin-peptide nanocomplexes enhance transcytosis from cellular depots and improve diabetic blood glucose control
Authors: Sahrish Rehmani, Christopher M. McLaughlin, Hoda M. Eltaher, R. Charlotte Moffett, Peter R. Flatt, James E. Dixon
Journal: Journal of Controlled Release (2023)

Insulin regulates blood glucose levels, and is the mainstay for the treatment of type-1 diabetes and type-2 when other drugs provide inadequate control. Therefore, effective oral Insulin delivery would be a significant advance in drug delivery. Herein, we report the use of the modified cell penetrating peptide (CPP) platform, Glycosaminoglycan-(GAG)-binding-enhanced-transduction (GET), as an efficacious transepithelial delivery vector in vitro and to mediate oral Insulin activity in diabetic animals. Insulin can be conjugated with GET via electrostatic interaction to form nanocomplexes (Insulin GET-NCs). These NCs (size and charge; 140 nm, +27.10 mV) greatly enhanced Insulin transport in differentiated in vitro intestinal epithelium models (Caco2 assays; >22-fold increased translocation) with progressive and significant apical and basal release of up-taken Insulin. Delivery resulted in intracellular accumulation of NCs, enabling cells to act as depots for subsequent sustained release without affecting viability and barrier integrity. Importantly Insulin GET-NCs have enhanced proteolytic stability, and retained significant Insulin biological activity (exploiting Insulin-responsive reporter assays). Our study culminates in demonstrating oral delivery of Insulin GET-NCs which can control elevated blood-glucose levels in streptozotocin (STZ)-induced diabetic mice over several days with serial dosing. As GET promotes Insulin absorption, transcytosis and intracellular release, along with in vivo function, our simplistic complexation platform could allow effective bioavailability of other oral peptide therapeutics and help transform the treatment of diabetes.
Nanosized Silk‐Magnesium Complexes for Tissue Regeneration
Authors: Zhaozhao Ding, Weinan Cheng, Lutong Liu, Gang Xu, Qiang Lu, David L. Kaplan
Journal: Advanced Healthcare Materials (2023)

Abstract Metal ions provide multifunctional signals for cell and tissue functions, including regeneration. Inspired by metal−organic frameworks (MOFs), nanosized silk protein aggregates with a high negative charge density are used to form stable silk−magnesium ion complexes. Magnesium ions (Mg ions) are added directly to silk nanoparticle solutions, inducing gelation through the formation of silk‐Mg coordination complexes. The Mg ions are released slowly from the nanoparticles through diffusion, with sustained release via tuning the degradation or dissolution of the nanosized silk aggregates. Studies in vitro reveal a dose‐dependent influence of Mg ions on angiogenic and anti‐inflammatory functions. Silk‐Mg ion complexes in the form of hydrogels also stimulate tissue regeneration with a reduced formation of scar tissue in vivo, suggesting potential utility in tissue regeneration.
Prognostic Value of Hemodynamic Gain Index in Patients With Heart Failure With Reduced Ejection Fraction
Authors: Thanat Chaikijurajai, J. Emanuel Finet, Timothy Engelman, Yuping Wu, Pieter Martens, Erik Van Iterson, Vicente Morales-Oyarvide, Justin L. Grodin, W.H. Wilson Tang
Journal: JACC Heart Failure (2023)
Health Disparities in Peripheral Artery Disease: A Scientific Statement From the American Heart Association
Authors: Matthew A. Allison, David G. Armstrong, Philip P. Goodney, Naomi M. Hamburg, Lee Kirksey, Kristie J. Lancaster, Carlos I. Mena-Hurtado, Sanjay Misra, Diane J. Treat-Jacobson, Khendi T. White Solaru
Journal: Circulation (2023)

Peripheral artery disease (PAD) affects 200 million individuals worldwide. In the United States, certain demographic groups experience a disproportionately higher prevalence and clinical effect of PAD. The social and clinical effect of PAD includes higher rates of individual disability, depression, minor and major limb amputation along with cardiovascular and cerebrovascular events. The reasons behind the inequitable burden of PAD and inequitable delivery of care are both multifactorial and complex in nature, including systemic and structural inequity that exists within our society. Herein, we present an overview statement of the myriad variables that contribute to PAD disparities and conclude with a summary of potential novel solutions.
Diagnostic Impact and Prognostic Value of Cardiac Magnetic Resonance in Patients With Ventricular Arrhythmias
Authors: Yin Ge, Panagiotis Antiochos, Ayako Seno, Iqra Qamar, Ron Blankstein, Michael Steigner, Ayaz Aghayev, Michael Jerosch-Herold, Usha B. Tedrow, William G. Stevenson, Raymond Y. Kwong
Journal: JACC. Cardiovascular imaging (2023)
Post-exposure vaccine effectiveness and contact management in the mpox outbreak, Madrid, Spain, May to August 2022
Authors: Laura Montero Morales, José Francisco Barbas del Buey, Marcos Alonso García, Noelia Cenamor Largo, Alba Nieto Juliá, María C Vázquez Torres, Susana Jiménez Bueno, Andrés Aragón Peña, Elisa Gil Montalbán, Jesús Íñigo Martínez, María Alonso Colón, Araceli Arce Arnáez
Journal: Eurosurveillance (2023)

BackgroundAppropriate vaccination strategies have been key to controlling the outbreak of mpox outside endemic areas in 2022, yet few studies have provided information on mpox vaccine effectiveness (VE).AimTo assess VE after one dose of a third-generation smallpox vaccine against mpox when given as post-exposure prophylaxis (PEP) within 14 days.MethodsA survival analysis in a prospective cohort of close contacts of laboratory-confirmed mpox cases was conducted from the beginning of the outbreak in the region of Madrid in May 2022. The study included contacts of cases in this region diagnosed between 17 May and 15 August 2022. Follow up was up to 49 days. A multivariate proportional hazard model was used to evaluate VE in the presence of confounding and interaction.ResultsInformation was obtained from 484 close contacts, of which 230 were vaccinated within 14 days of exposure. Of the close contacts, 57 became ill during follow-up, eight vaccinated and 49 unvaccinated. The adjusted effectiveness of the vaccine was 88.8% (95% CI: 76.0-94.7). Among sexual contacts, VE was 93.6% (95% CI: 72.1-98.5) for non-cohabitants and 88.6% (95% CI: 66.1-96.2) for cohabitants.ConclusionPost-exposure prophylaxis of close contacts of mpox cases is an effective measure that can contribute to reducing the number of cases and eventually the symptoms of breakthrough infections. The continued use of PEP together with pre-exposure prophylaxis by vaccination and other population-targeted prevention measures are key factors in controlling an mpox outbreak.
Vendor Independent Coronary Calcium Scoring Improves Individual Risk Assessment
Authors: Niels R. van der Werf, Magdalena M. Dobrolinska, Marcel J.W. Greuter, Martin J. Willemink, Dominik Fleischmann, Daniel Bos, Riemer H.J.A. Slart, Matthew Budoff, Tim Leiner
Journal: JACC. Cardiovascular imaging (2023)
Mild Hypercapnia or Normocapnia after Out-of-Hospital Cardiac Arrest
Authors: Glenn Eastwood, Alistair D. Nichol, Carol Hodgson, Rachael L. Parke, Shay McGuinness, Niklas Nielsen, Stephen Bernard, Markus B. Skrifvars, Dion Stub, Fabio S. Taccone, John Archer, Demetrios Kutsogiannis, Josef Dankiewicz, Gisela Lilja, Tobias Cronberg, Hans Kirkegaard, Gilles Capellier, Giovanni Landoni, Janneke Horn, Theresa Olasveengen, Yaseen Arabi, Yew Woon Chia, Andrej Markota, Matthias Hænggi, Matt P. Wise, Anders M. Grejs, Steffen Christensen, Heidi Munk-Andersen, Asger Granfeldt, Geir Ø. Andersen, Eirik Qvigstad, Arnljot Flaa, Matthew Thomas, Katie Sweet, Jeremy Bewley, Minna Bäcklund, Marjaana Tiainen, Manuela Iten, Anja Levis, Leah Peck, James Walsham, Adam Deane, Angajendra Ghosh, Filippo Annoni, Yan Chen, David Knight, Eden Lesona, Haytham Tlayjeh, Franc Svenšek, Peter J. McGuigan, Jade Cole, David Pogson, Matthias P. Hilty, Joachim P. Düring, Michael J. Bailey, Eldho Paul, Bridget Ady, Kate Ainscough, Anna Hunt, Sinéad Monahan, Tony Trapani, Ciara Fahey, Rinaldo Bellomo
Journal: New England Journal of Medicine (2023)

Guidelines recommend normocapnia for adults with coma who are resuscitated after out-of-hospital cardiac arrest. However, mild hypercapnia increases cerebral blood flow and may improve neurologic outcomes.We randomly assigned adults with coma who had been resuscitated after out-of-hospital cardiac arrest of presumed cardiac or unknown cause and admitted to the intensive care unit (ICU) in a 1:1 ratio to either 24 hours of mild hypercapnia (target partial pressure of arterial carbon dioxide [Paco2], 50 to 55 mm Hg) or normocapnia (target Paco2, 35 to 45 mm Hg). The primary outcome was a favorable neurologic outcome, defined as a score of 5 (indicating lower moderate disability) or higher, as assessed with the use of the Glasgow Outcome Scale-Extended (range, 1 [death] to 8, with higher scores indicating better neurologic outcome) at 6 months. Secondary outcomes included death within 6 months.A total of 1700 patients from 63 ICUs in 17 countries were recruited, with 847 patients assigned to targeted mild hypercapnia and 853 to targeted normocapnia. A favorable neurologic outcome at 6 months occurred in 332 of 764 patients (43.5%) in the mild hypercapnia group and in 350 of 784 (44.6%) in the normocapnia group (relative risk, 0.98; 95% confidence interval [CI], 0.87 to 1.11; P = 0.76). Death within 6 months after randomization occurred in 393 of 816 patients (48.2%) in the mild hypercapnia group and in 382 of 832 (45.9%) in the normocapnia group (relative risk, 1.05; 95% CI, 0.94 to 1.16). The incidence of adverse events did not differ significantly between groups.In patients with coma who were resuscitated after out-of-hospital cardiac arrest, targeted mild hypercapnia did not lead to better neurologic outcomes at 6 months than targeted normocapnia. (Funded by the National Health and Medical Research Council of Australia and others; TAME ClinicalTrials.gov number, NCT03114033.).